Assessing of plasma levels of iron, zinc and copper in Iranian Parkinson's disease

Authors

1 Department of Medical Sciences, Islamic Azad University, Najafabad Branch, Isfahan; Isfahan Neurosciences Research Center, AlZahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Medical Sciences, Islamic Azad University, Najafabad Branch, Isfahan, India

3 Isfahan Neurosciences Research Center, AlZahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

4 Isfahan Health Research Station, Tehran University of Medical Sciences, Tehran; National Institute of Health Research, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Background: Trace elements have long been suspected to be involved in Parkinson's disease (PD) pathogenesis, but their exact roles have been remained controversial. In this study, we assessed the levels of copper (Cu), iron (Fe) and zinc (Zn) in different stage of PD patients.
Materials and Methods: Serum concentrations of iron, copper and zinc were measured in 109 patients with PD by colorimetric methods. Staging of the disease was evaluated according to Hoehn and Yahr (H and Y) and Unified PD Rating Scale III (UPDRS).




Results: Severity values of PD measured by UPRDSIII and HY stages with mean ± SD were 22.9 ± 1.81 and 1.8 ± 1.1, respectively. Mean ± SD values of iron, zinc and copper are 100.7 ± 289.2, 68.3 ± 5.32, and 196.8 ± 162.1 μg/dl, respectively. Serum iron level in most of the patients was normal (76.6%). Whereas zinc concentration in most participants was below the normal range (64.5%) and serum Cu in the majority of patients had a high normal concentration (42.7%) and did not significantly differ among various PD stages.
Conclusion: The result of this study does not confirm strong correlation between PD stages and serum levels of tested trace elements. The actual correlations between these elements and PD and whether modulating of these agents levels could be an effective approach in the treatment of this disease remain to be elucidated.

Keywords

1.
Ikawa M, Okazawa H, Kudo T, Kuriyama M, Fujibayashi Y, Yoneda M. Evaluation of striatal oxidative stress in patients with Parkinson's disease using [62Cu] ATSM PET. Nucl Med Biol 2011;38:945-51.  Back to cited text no. 1
    
2.
Grabrucker AM, Rowan M, Garner CC. Brain-delivery of Zinc-ions as potential treatment for neurological diseases: Mini review. Drug Deliv Lett 2011;1:13-23.  Back to cited text no. 2
    
3.
Crichton RR, Ward RJ. Metal-based neurodegeneration. England: John Wiley and Sons; 2006.  Back to cited text no. 3
    
4.
Wolozin B, Golts N. Iron and Parkinson's disease. Neuroscientist 2002;8:22-32.  Back to cited text no. 4
    
5.
Younes-Mhenni S, Aissi M, Mokni N, Boughammoura-Bouatay A, Chebel S, Frih-Ayed M, et al. Serum copper, zinc and selenium levels in Tunisian patients with Parkinson's disease. Tunis Med 2013;91:402-5.  Back to cited text no. 5
[PUBMED]    
6.
Binolfi A, Rodriguez EE, Valensin D, D'Amelio N, Ippoliti E, Obal G, et al. Bioinorganic chemistry of Parkinson's disease: Structural determinants for the copper-mediated amyloid formation of alpha-synuclein. Inorg Chem 2010;49:10668-79.  Back to cited text no. 6
    
7.
Jiménez-Jiménez FJ, Fernández-Calle P, Martínez-Vanaclocha M, Herrero E, Molina JA, Vázquez A, et al. Serum levels of zinc and copper in patients with Parkinson's disease. J Neurol Sci 1992;112:30-3.  Back to cited text no. 7
    
8.
Younes-Mhenni S, Aissi M, Mokni N, Boughammoura-Bouatay A, Chebel S, Frih-Ayed M, et al. Serum copper, zinc and selenium levels in Tunisian patients with Parkinson's disease. Tunis Med 2013;91:402- 5.  Back to cited text no. 8
[PUBMED]    
9.
Kay AR, Tóth K. Is zinc a neuromodulator? Sci Signal 2008;1:re3.  Back to cited text no. 9
    
10.
Kanninen KM, Grubman A, Meyerowitz J, Duncan C, Tan JL, Parker SJ, et al. Increased zinc and manganese in parallel with neurodegeneration, synaptic protein changes and activation of Akt/GSK3 signaling in ovine CLN6 neuronal ceroid lipofuscinosis. PLoS One 2013;8:e58644.  Back to cited text no. 10
    
11.
Mizuno D, Kawahara M. The molecular mechanisms of zinc neurotoxicity and the pathogenesis of vascular type senile dementia. Int J Mol Sci 2013;14:22067-81.  Back to cited text no. 11
    
12.
Hegde ML, Shanmugavelu P, Vengamma B, Rao TS, Menon RB, Rao RV, et al. Serum trace element levels and the complexity of inter-elements relations in patients with Parkinson's disease. J Trace Elem Med Biol 2004;18:163-71.  Back to cited text no. 12
    
13.
Brewer GJ, Kanzer SH, Zimmerman EA, Molho ES, Celmins DF, Heckman SM, et al. Subclinical zinc deficiency in Alzheimer's disease and Parkinson's disease. Am J Alzheimers Dis Other Demen 2010;25:572-5.  Back to cited text no. 13
    
14.
Forsleff L, Schauss AG, Bier ID, Stuart S. Evidence of functional zinc deficiency in Parkinson's disease. J Altern Complement Med 1999;5:57-64.  Back to cited text no. 14
    
15.
Zhao HW, Lin J, Wang XB, Cheng X, Wang JY, Hu BL, et al. Assessing plasma levels of selenium, copper, iron and zinc in patients of Parkinson's disease. PLoS One 2013;8:e83060.  Back to cited text no. 15
    
16.
Hoehn MM, Yahr MD, Parkinsonism: Onset, progression, and mortality. 1967. Neurology 2001;57(Suppl 3):S11-26.  Back to cited text no. 16
    
17.
Goetz CG. Movement disorder society-unified Parkinson's disease rating scale (MDS-UPDRS): A new scale for the evaluation of Parkinson's disease. Rev Neurol 2010;166:1-4.  Back to cited text no. 17
[PUBMED]    
18.
Mariani S, Ventriglia M, Simonelli I, Donno S, Bucossi S, Vernieri F, et al. Fe and Cu do not differ in Parkinson's disease: A replication study plus meta-analysis. Neurobiol Aging 2013;34:632-3.  Back to cited text no. 18
    
19.
Ahmed SS, Santosh W. Metallomic profiling and linkage map analysis of early Parkinson's disease: A new insight to aluminum marker for the possible diagnosis. PLoS One 2010;5:e11252.  Back to cited text no. 19
    
20.
Fukushima T, Tan X, Luo Y, Kanda H. Serum vitamins and heavy metals in blood and urine, and the correlations among them in Parkinson's disease patients in China. Neuroepidemiology 2011;36:240-4.  Back to cited text no. 20
    
21.
Dexter DT, Carayon A, Javoy-Agid F, Agid Y, Wells FR, Daniel SE, et al. Alterations in the levels of iron, ferritin and other trace metals in Parkinson's disease and other neurodegenerative diseases affecting the basal ganglia. Brain 1991;114:1953-75.  Back to cited text no. 21
    
22.
Mann VM, Cooper JM, Daniel SE, Srai K, Jenner P, Marsden CD, et al. Complex I, iron, and ferritin in Parkinson's disease substantia nigra. Ann Neurol 1994;36:876-81.  Back to cited text no. 22
    
23.
Lotfipour AK, Wharton S, Schwarz ST, Gontu V, Schäfer A, Peters AM, et al. High resolution magnetic susceptibility mapping of the substantia nigra in Parkinson's disease. J Magn Reson Imaging 2012;35:48-55.  Back to cited text no. 23
    
24.
Logroscino G, Marder K, Graziano J, Freyer G, Slavkovich V, LoIacono N, et al. Altered systemic iron metabolism in Parkinson's disease. Neurology 1997;49:714-7.  Back to cited text no. 24
    
25.
Qureshi GA, Qureshi AA, Memon SA, Parvez SH. Impact of selenium, iron, copper and zinc in on/off Parkinson's patients on L-dopa therapy. J Neural Transm Suppl 2006;229-36.  Back to cited text no. 25
    
26.
Ling H, Bhidayasiri R. Reduced serum caeruloplasmin levels in non-wilsonian movement disorders. Eur Neurol 2011;66:123-7.  Back to cited text no. 26
    
27.
Zhao HW, Lin J, Wang XB, Cheng X, Wang JY, Hu BL, et al. Assessing plasma levels of selenium, copper, iron and zinc in patients of Parkinson's disease. PLoS One 2013;8:e83060.  Back to cited text no. 27
    
28.
King ER, Wong KK. Insulin-like growth factor: Current concepts and new developments in cancer therapy. Recent Pat Anticancer Drug Discov 2012;7:14-30.  Back to cited text no. 28
    
29.
Pall HS, Williams AC, Blake DR, Lunec J, Gutteridge JM, Hall M, et al. Raised cerebrospinal-fluid cooper concentration in Parkinson's disease. Lancet 1987;2:238-41.  Back to cited text no. 29
[PUBMED]    
30.
Mariani S, Ventriglia M, Simonelli I, Donno S, Bucossi S, Vernieri F, et al. Fe and Cu do not differ in Parkinson's disease: A replication study plus meta-analysis. Neurobiol Aging 2013;34:632-3.  Back to cited text no. 30
    
31.
Nikam S, Nikam P, Ahaley SK, Sontakke AV. Oxidative stress in Parkinson's disease. Indian J Clin Biochem 2009;24:98-101.  Back to cited text no. 31
    
32.
Jiménez-Jiménez FJ, Molina JA, Aguilar MV, Meseguer I, Mateos-Vega CJ, González-Muñoz MJ, et al. Cerebrospinal fluid levels of transition metals in patients with Parkinson's disease. J Neural Transm 1998;105:497-505.  Back to cited text no. 32
    
33.
Miao L, St Clair DK. Regulation of superoxide dismutase genes: Implications in disease. Free Radic Biol Med 2009;47:344-56.  Back to cited text no. 33
    
34.
Szyrwiel L, Pap JS, Malinka W, Szewczuk Z, Kotynia A, Brasun J. Interactions of anti-Parkinson drug benserazide with Zn (II), Cu (II), Fe (II) ions. J Pharm Biomed Anal 2013;76:36-43.  Back to cited text no. 34
    
35.
Gellein K, Syversen T, Steinnes E, Nilsen TI, Dahl OP, Mitrovic S, et al. Trace elements in serum from patients with Parkinson's disease – A prospective case control study: The Nord-Trondelag Health Study (HUNT). Brain Res 2008;1219:111-5.  Back to cited text no. 35
    
36.
Tokuda E, Ono S, Ishige K, Watanabe S, Okawa E, Ito Y, et al. Ammonium tetrathiomolybdate delays onset, prolongs survival, and slows progression of disease in a mouse model for amyotrophic lateral sclerosis. Exper Neurol 2008;213:122-8.  Back to cited text no. 36
    
37.
Kim J, Kim TY, Hwang JJ, Lee JY, Shin JH, Gwag BJ, et al. Accumulation of labile zinc in neurons and astrocytes in the spinal cords of G93A SOD-1 transgenic mice. Neurobiol Dis 2009;34:221-9.  Back to cited text no. 37
    
38.
Hozumi I, Asanuma M, Yamada M, Uchida Y. Metallothioneins and neurodegenerative diseases. J Health Science 2004;50:323-31.  Back to cited text no. 38